Malaria is one of the most ancient infectious diseases that still has strong impact upon human health. According to the World Health Organization (WHO), about 40% of the world's population are still under the threat of malaria, which has been distributed to more than 100 countries. Today, there are about 300–500 million malaria cases every year, of which about 3 million die from it. Moreover, because of the emergence and quick spread diffusion of drug resistance by plasmodia and mosquito vector, malaria has not been effectively controlled. On the contrary, it is likely to stage a comeback. Thus the expansion of a global project to control malaria has become one of the emphatic study fields of WHO in the new century.
People can depend upon or expect to achieve breakthrough in controlling malaria through three main pathways: anti-malaria drugs, malaria vaccines and mosquito vector control. However, anti-malaria drugs and mosquito vector control are facing great difficulties and challenges, which have been the result of the emergence and spread of drug resistance of plasmodia and mosquito. Although the malaria vaccine with application value has not become visible at present, it is still generally believed that the development of malaria vaccine is an important pathway for human beings to control and even eradicate malaria.
Many studies have indicated that the prevention of malaria could be achieved through the development of effective vaccines. For example, volunteers immunized by inactivated sporozoit could be completely protected against subsequent challenge of Plasmodium falciparum. Also, the mouse immunized by murine Plasmodium recombinant antigen could be completely protected against subsequent infection attacks from homogenous Plasmodium. In addition, epidemiological studies on malaria also demonstrates that the population dying from malaria is mainly those having no immunity against malaria, e.g. children living in malaria endemic areas and population from malaria non-endemic areas entering malaria endemic areas, while adults in malaria endemic areas seldom die of it. If inoculating these people having no specific immunity with effective vaccines, it could be expected that the specific immunity could be induced similar to that of the adults from malaria endemic areas, and thus the objective to prevent malaria and reduce malaria mortality can be achieved. Hence, the development of malaria vaccines has become the hot topic in the world nowadays.
In the development of malaria vaccines, the studies upon two candidate vaccines have ever been widely noticed, and one of which is anti-sporozoit vaccine. This vaccine could induce immunity to inhibit invasion of sporozoit into hepatic cells. However, subsequent clinical trials do not show good efficacy. According to the analysis, the vaccine could just generate immunity against sporozoit, but even if only a few sporozoit escapes the immune attack of the vaccine and survive, they could invade hepatic cells and develop and proliferate to generate thousands of merozoites enough to cause disease in hosts. The other one is SPf66 polyvalence synthetic peptide vaccine. This vaccine is a 45-peptide polymer made of three 10-peptide epitopes separately linked through hydrophobic amino acids (Patarroyo, M. E., et al., Induction of protective immunity against experimental infection with malaria Suing Synthetic peptides, Nature; 328: 629, 1987). This vaccine achieved good immune protection against challenge of Plasmodium falciparum in Aotus monkeys. However, an ideal clinical protection has not been achieved in the subsequent clinical trials in Africa, South-east Asia and Latin America, and thus no applicable value was established. The reason of failure of this vaccine may lie in the fact that SPf 66 only has 45 peptides. In such a short, chained peptide sequence, there may not be T cell epitopes enough for most individual MHC molecules to bind, which results in the prevention of antigen presentation.
Although the studies on malaria vaccines using biotechnology have been conducted for about 20 years, a vaccine with application value has yet to become available. It can be seen that the breakthrough in malaria vaccines still calls for further confirmation on the candidate antigens providing protection against malaria, clarification on the immunological mechanism of protection effect, and establishment of new strategies about malaria vaccine development.
Thus, it is urgently required in the art to develop effective immunogens and related vaccines against malaria.